Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of monoamine biosynthetic enzymes were measured in brain regions of several hypertensive rat models at various ages. The types of hypertensive rats were the spontaneously hypertensive rat (SHR) and a stroke-prone substrain of the SHR as well as DOCA-salt and renal hypertensive rats. The genetically hypertensive rats had significantly elevated blood pressures as compared to the Wistar-Kyoto control rat after 5 weeks of age. During the early development of hypertension in the SHR, the activities of tyrosine hydroxylase in the hypothalamus and corpus striatum and of dopamine-beta-hydroxylase in the hypothalamus and pons-medulla were significantly higher than in the control rats. Tryptophan-hydroxylase was also elevated in the hypothalamus in SHR. From 3 to 8 weeks of age there appeared to be a significant correlation between hypothalamic dopamine-beta-hydroxylase activity and blood pressure in the hypertensive rats. In contrast, the activities of tyrosine hydroxylase and dopamine-beta-hydroxylase were slightly decreased in the DOCA-salt and renal hypertensive rats. It is suggested that noradrenergic or adrenergic neurons in the hypothalamus may participate in the initiation of elevated blood pressure in the genetic, but not in the DOCA-salt or renal hypertensive rats.
 ...
PMID:Regional changes in the activities of aminergic biosynthetic enzymes in the brains of hypertensive rats. 1 54

Mongolian gerbils were treated with alpha-methyl-para-tyrosine methyl ester (AMPT, a tyrosine hydroxylase inhibitor), in order to decrease brain levels of catecholamines. Six hours later, unilateral ischemic stroke was induced by ligation of the left common carotid artery. The delayed degeneration of nerve terminals was studied sixteen hours later by measuring the high-affinity uptake of radiolabeled transmitters by isolated synaptosomes. Dopamine, serotonin and glutamate terminals were studied. AMPT-treated gerbils were compared to untreated (no AMPT) animals; 220 gerbils were studied. AMPT pretreatment (100, 250 and 400 mg/kg) produced a dose-dependent protection of all three types of nerve terminals. In the absence of AMPT pretreatment, the uptake of radiolabeled transmitters by the ischemic hemisphere, expressed as a percentage of that seen in the contralateral (unaffected) side of the brain, was as follows (mean +/- SEM): 27.3 +/- 5.2% for dopamine terminals, 49.5 +/- 6.2% for serotonin terminals, and 42.7 +/- 5.3% for glutamate terminals. Protection was essentially complete at a dose of 400 mg AMPT per kg. The number of animals with significant damage to nerve terminals was reduced from 38.5% in untreated animals to 11.1% in animals treated with AMPT 400 mg/kg. Although the nerve terminals were protected, gerbils still showed the behavioral signs of unilateral stroke due to the permanent occlusion of the left carotid. These results indicate that endogenous dopamine may play a significant role in ischemic damage to nerve terminals in the cerebrum.
Stroke
PMID:Nerve terminal damage in cerebral ischemia: protective effect of alpha-methyl-para-tyrosine. 286 54

The concentration of noradrenaline was measured in various regions of the brain and spinal cord of spontaneously hypertensive rats, stroke-prone spontaneously hypertensive rats and normotensive Wistar/Kyoto controls. Elevated noradrenaline levels were consistently found in the pons, cerebellum and spinal cord of the two hypertensive strains. These changes occurred both in young rats, during the early development of hypertension, and in mature rats, after establishment of the hypertension. The increases of cerebellar and spinal noradrenaline in mature stroke-prone rats could not be reversed by lowering blood pressure with hydralazine. The increased noradrenaline concentrations were not accompanied by increased tyrosine hydroxylase activity in the hypertensive rats. However, comparisons of noradrenaline turnover made using the catecholamine synthesis inhibitor, alpha-methyltyrosine, indicate an increased turnover of spinal noradrenaline in both hypertensive strains after establishment of hypertension. The results suggest that the activity of spinal noradrenergic nerves is augmented in genetically hypertensive animals.
 ...
PMID:Content and turnover of noradrenaline in spinal cord and cerebellum of spontaneously hypertensive and stroke-prone rats. 611 79

We have developed a stroke model involving middle cerebral artery occlusion in the rat which elicits changes in cardiac and autonomic variables that are similar to those observed clinically. It is likely that these neurogenic autonomic responses are mediated by changes in neurotransmitter systems subsequent to the stroke. This possibility was investigated by examining changes in immunohistochemical staining for tyrosine hydroxylase, neuropeptide Y, leu-enkephalin, neurotoxins and dynorphin following middle cerebral artery occlusion in the rat. Computerized image analysis was used to provide semi-quantitative measurements of the changes. The ischemic region was centered primarily in the insular cortex. The results indicate that there are significant increases in immunostaining for tyrosine hydroxylase and neuropeptide Y in the insular cortex within the peri-infarct region. Neuropeptide Y staining was also significantly increased in the basolateral nucleus of the amygdala, ipsilateral to the middle cerebral artery occlusion, which did not appear to be included in the infarct. Leu-enkephalin, neurotensin and dynorphin staining was significantly elevated in the central nucleus of the amygdala ipsilateral to the occlusion of the middle cerebral artery. These neurochemical changes are discussed as possible mechanisms mediating the cardiac and autonomic consequences of stroke or as part of a process to provide neuro-protection following focal cerebral ischemia.
 ...
PMID:Neurochemical changes following occlusion of the middle cerebral artery in rats. 854 80

Neurones in the rat substantia nigra compacta (SNC) are initially resistant to transient forebrain ischaemia in contrast to vulnerable neurones in the striatum that die within 24 h. Animals were exposed to 20 min of four vessel occlusion and killed 1 and 3 weeks after reperfusion. All ischaemic animals had striatal neurone loss. Analysis of the number of tyrosine hydroxylase immunoreactive neurones (THir) in the SNC was comparable between controls and ischaemic animals killed 1 week after reperfusion. However, there was a significant reduction in THir neurone number (24%), SNC volume (17%), and THir dendritic arborization in the substantia nigra reticulata (SNR) that occurred 3 weeks after reperfusion, despite the persistence of THir axons in the striatum. Detailed morphological analysis of areas distant from the initial ischaemic injury suggest delayed degeneration may play an important role in the brain's response to ischaemia, and may provide insights for clinical stroke treatment and management.
 ...
PMID:Delayed histopathological neuronal damage in the substantia nigra compacta (nucleus A9) after transient forebrain ischaemia. 898 15

Recently, we have shown increases in the immunoreactivity for neuropeptide Y and tyrosine hydroxylase in the insular cortex surrounding the focal infarction after middle cerebral artery occlusion. In addition, the immunoreactivity for neuropeptide Y, leucine-enkephalin, dynorphin, and neurotensin increased ipsilaterally in the amygdala. Increases in immunoreactivity were observed in nerve terminals and fibers; changes in the neuropeptides were maximal 3 days after stroke. Local excitotoxic injury of the insular cortex also elicited similar neuropeptide changes unilaterally in the same regions. In this study, immunohistochemistry was used following intracerebroventricular injection of colchicine and stroke to determine whether blockade of axonal transport would prevent these neurochemical changes. These experiments would also locate the putative cellular origins of the neurochemicals involved. Control rats received either colchicine injection or middle cerebral artery occlusion alone. Injection of colchicine enhanced the periinfarct increase in neuropeptide Y but did not alter the increase in tyrosine hydroxylase. The neuropeptide Y increase was observed in local cortical neurons. Colchicine prevented the increases in immunoreactivity for the neuropeptides in the amygdala on the side of stroke, although there were small perikarya that showed immunoreactivity for these neuropeptides within the amygdala on both sides. We conclude that local cortical neurons are responsible for the increase in neuropeptide Y in the periinfarct region, that the cortical increase in tyrosine hydroxylase is not dependent on fast axonal transport, and that axonal transport of signals from the insular cortex to the amygdala is critical in mediating the amygdalar neuropeptide changes seen after stroke.
 ...
PMID:Colchicine affects cortical and amygdalar neurochemical changes differentially after middle cerebral artery occlusion in rats. 933 Nov 69

The clinical findings on neural transplantation for Parkinson's disease (PD) reported thus far are promising but many issues must be addressed before neural transplantation can be considered a routine therapeutic option for PD. The future of neural transplantation for the treatment of neurological disorders may rest in the discovery of a suitable alternative cell type for fetal tissue. One such alternative may be neurons derived from a human teratocarcinoma (hNT). hNT neurons have been shown to survive and integrate within the host brain following transplantation and provide functional recovery in animal models of stroke and Huntington's disease. In this study, we describe the transplantation of hNT neurons in the substantia nigra (SN) and striatum of the rat model for PD. Twenty-seven rats were grafted with one of three hNT neuronal products; hNT neurons, hNT-DA neurons, or lithium chloride (LiCl) pretreated hNT-DA neurons. Robust hNT grafts could be seen with anti-neural cell adhesion molecule and anti-neuron-specific enolase immunostaining. Immunostaining for tyrosine hydroxylase (TH) expression revealed no TH-immunoreactive (THir) neurons in any animals with hNT neuronal grafts. THir cells were observed in 43% of animals with hNT-DA neuronal grafts and all animals with LiCl pretreated hNT-DA neuronal grafts (100%). The number of THir neurons in these animals was low and not sufficient to produce significant functional recovery. In summary, this study has demonstrated that hNT neurons survive transplantation and express TH in the striatum and SN. Although hNT neurons are promising as an alternative to fetal tissue and may have potential clinical applications in the future, further improvements in enhancing TH expression are needed.
 ...
PMID:Intrastriatal and intranigral grafting of hNT neurons in the 6-OHDA rat model of Parkinson's disease. 1073 41

Multiple doses of the dietary supplement L-ephedrine can cause severe hyperthermia and modest dopamine depletions in the rat brain. Since D-amphetamine treatment can result in neurodegeneration, the potential of L-ephedrine to produce similar types of degeneration was investigated. Adult male rats, some implanted in the caudate/putamen (CPu) for microdialysis, were given four doses of 25 mg/kg L-ephedrine or 5 mg/kg D-amphetamine (2 h between doses) at an ambient temperature of 23 degrees C. L-ephedrine-induced degeneration in the forebrain was dependent on the degree of hyperthermia. Layer IV of the parietal cortex was the most sensitive to L-ephedrine treatment with peak body temperatures of at most 40.0 degrees C necessary to produce degeneration. Extensive neurodegeneration in the parietal cortex after L-ephedrine treatment was as pronounced as that previously described for D-amphetamine treatment and also occurred in the intralaminar, ventromedial and ventrolateral thalamic nuclei in rats with severe hyperthermia (peak body temperatures>41.0 degrees C). The neurodegeneration induced by L-ephedrine may have resulted in part from excitotoxic mechanisms involving the indirect pathways of the basal ganglia and related areas. No differences were observed between microdialysis and non-implanted rats with respect to degree of tyrosine hydroxylase (TH) loss in the CPu after either D-amphetamine or L-ephedrine treatment. However, neurodegeneration resulting from D-amphetamine and L-ephedrine was reduced in the microdialysis animals in the hemisphere ipsilateral to the probe, which raises concerns when using the technique of in vivo microdialysis to evaluate neurodegeneration. The results of this study, in conjunction with human clinical evaluation of ephedrine neurotoxicity, indicate that regionally specific damage may occur in the cortex of some humans exposed to ephedrine in the absence of stroke or hemorrhage.
 ...
PMID:L-ephedrine-induced neurodegeneration in the parietal cortex and thalamus of the rat is dependent on hyperthermia and can be altered by the process of in vivo brain microdialysis. 1170 Dec 34

Cytidine-5'-diphosphocholine (citicoline or CDP-choline), an intermediate in the biosynthesis of phosphatidylcholine (PtdCho), has shown beneficial effects in a number of CNS injury models and pathological conditions of the brain. Citicoline improved the outcome in several phase-III clinical trials of stroke, but provided inconclusive results in recent clinical trials. The therapeutic action of citicoline is thought to be caused by stimulation of PtdCho synthesis in the injured brain, although the experimental evidence for this is limited. This review attempts to shed some light on the properties of citicoline that are responsible for its effectiveness. Our studies in transient cerebral ischemia suggest that citicoline might enhance reconstruction (synthesis) of PtdCho and sphingomyelin, but could act by inhibiting the destructive processes (activation of phospholipases). Citicoline neuroprotection may include: (i) preserving cardiolipin (an exclusive inner mitochondrial membrane component) and sphingomyelin; (ii) preserving the arachidonic acid content of PtdCho and phosphatidylethanolamine; (iii) partially restoring PtdCho levels; (iv) stimulating glutathione synthesis and glutathione reductase activity; (v) attenuating lipid peroxidation; and (vi) restoring Na(+)/K(+)-ATPase activity. These observed effects of citicoline could be explained by the attenuation of phospholipase A(2) activation. Based on these findings, a singular unifying mechanism has been hypothesized. Citicoline also provides choline for synthesis of neurotransmitter acetylcholine, stimulation of tyrosine hydroxylase activity and dopamine release.
 ...
PMID:Citicoline: neuroprotective mechanisms in cerebral ischemia. 1179 39

Cyclosporine-A (CsA) is neuroprotective in animal models of Parkinson's disease (PD), Huntington's disease and stroke. Because CsA does not easily cross the blood-brain barrier (BBB), high doses (i.e. >10 mg/kg in rats) and chronic administration may be necessary to produce beneficial effects. However, immunosuppressant side effects (including nephrotoxicity and hepatotoxicity) are associated with such CsA dosing regimens. The bradykinin B2 receptor agonist, Cereport (labradimil and formerly called RMP-7), transiently increases the permeability of the BBB to facilitate delivery of drugs to the CNS. Here we examined the effects of co-administration of CsA and Cereport in the unilateral 6-OHDA model of PD. Animals were pretreated with vehicle, CsA alone (1 mg/kg, a low dose without either immunosuppressive or neuroprotective effects, or 10 mg/kg, a high dose that produces both immunosuppression and neuroprotection), or CsA (1 mg/kg) in combination with Cereport (9 microg/kg). Behavioral analyses, using elevated body swing and amphetamine-induced rotational tests, revealed that a low dose of CsA was neuroprotective when combined with Cereport, but not when given alone. Tyrosine hydroxylase immunohistochemistry demonstrated that while near complete (>90%) depletions of nigral TH-ir neurons were noted in lesioned animals that received vehicle infusion or low-dose CsA alone, lesioned animals that received low-dose CsA+Cereport exhibited a significant sparing of nigral TH-ir neurons and a marked reduction in the loss of striatal TH-ir fibers. The safer and effective administration of lower doses of CsA combined with enhanced BBB permeability using Cereport, offers a novel way of producing protective effects in the CNS without the toxic liabilities of high-dose CsA.
 ...
PMID:Bradykinin receptor agonist facilitates low-dose cyclosporine-A protection against 6-hydroxydopamine neurotoxicity. 1244 88


1 2 3 4 5 6 Next >>